The 1993 discovery of small regulatory RNA molecules has taught us that the central dogma of molecular biology is much more complicated that originally thought. Rather than simply acting as a middle messenger in the quest to build proteins, it seemed that specialized RNA molecules could subtly mold a cellular phenotype through post- transcriptional regulation. Subsequent research has revealed that miRNA molecules are involved in critical regulatory networks such as differentiation, stress response, and oncogenesis. Known as microRNAs (miRNAs), these very small (approximately 17-26 nucleotides) molecules are difficult to manipulate from a molecular biology perspective. The work discussed herein will develop and commercialize a unique molecular biology technique that significantly simplifies the identification and quantitation of microRNAs. The method takes advantage of the fact that miRNAs are processed by RNaseIII enzymes, which leave a characteristic fingerprint on their cleavage products that can be recovered with the appropriate molecular }bait}. Results of a previous Phase I study are reported, in which proof of principle and initial results were obtained. The Phase II proposal outlines the experimental methodology that will refine the techniques, expand the portfolio, and design products that will bring the technology directly to bench scientists that lack any prior miRNA experience. This research effort will impact public health by providing researches with a next generation miRNA discovery tolls. Currently, there is a substantial effort in academic and industry laboratories to discovery miRNAs, as well as their specific functions. This research represents a tremendous opportunity to enhance our understanding of development, cell proliferation, differentiation, cell cycle, and disease (e.g., cancer and viral infections). The products developed under this SBIR will enable a broad class of life science researchers in miRNA discovery.